Increased corticotropin-releasing factor concentrations in the bed nucleus of the stria terminalis of anhedonic rats

Chronic mild stress in rats is an antidepressant-responsive model for anhedonic symptoms of major depression. Many patients with depression exhibit alterations in hypothalamic-pituitary-adrenal axis activity, and corticotropin-releasing factor (CRF) neuronal function. This study investigated the potential involvement of CRF and CRF receptors in the development of chronic mild stress-induced anhedonia in rats. Rats were subjected to 19 days of chronic mild stress, during which time anhedonia was periodically assessed by determining the threshold for self-stimulation of the ventral tegmental area. Anhedonic rats exhibited a 50% increase in CRF concentrations in the bed nucleus of the stria terminalis compared to control rats. There were no significant changes in hypothalamic-pituitary-adrenal axis activity, CRF or CRF1 receptor mRNA expression, or CRF receptor binding in the brain regions analyzed. Though preliminary, these results are consistent with the hypothesis that chronic stress-induced modulation of CRF function in specific brain structures such as the bed nucleus of the stria terminalis may contribute to the pathophysiology of depression. (C) 2000 Elsevier Science B.V. All rights reserved.